Multiple Sclerosis Podcast

Reproductive Rights, Maternal Health, and Menopause: Women and MS

Anne H. Cross, MD; Riley Bove, MD


February 02, 2023

This transcript has been edited for clarity.

Anne Cross, MD: Hello, I am Dr Anne Cross. Welcome to Medscape's InDiscussion series on multiple sclerosis. Women constitute the majority of MS patients, with an approximate 3-to-1 female-to-male ratio in MS, and many MS patients are diagnosed when in their twenties and thirties, which are prime ages for childbirth in women. In addition, these same women will experience hormonal changes over their lifespans, and eventually they'll go through menopause. Today, we will be discussing maternal health hormones and menopause in women with MS. I'd like to introduce you to my guest expert, Dr Riley Bove, who is an associate professor of neurology at University of California in San Francisco. She is also the founding director of the Program on Sex and Gender Enriched Neurology at UCSF. Welcome, Dr Bove. I think I'd like to start off, if you don't mind, with a question about your background and why you chose medicine and neurology and ultimately MS as a career.

Riley Bove, MD: Thanks so much, Dr Cross, for having me talk about this topic. And to your question, it did feel a little circuitous to me along the way, but in retrospect it was a direct arc and decision actually. As an undergraduate, I studied physical and medical anthropology. I was interested in what shapes the wellness and illness experiences and fascinated by the concept of local biology, how an individual's very body is shaped by the longitude or altitude where they grow up or the foods they eat, or their family composition or early childhood stressors, and especially how physiology is shaped by reproductive experiences. This took me on fieldwork and a journey within anthropology, but I eventually landed in medicine just because of the impetus to do something concrete about the health and illness experiences I was learning about. When I got to medical school, I was finding myself continuing to gravitate towards reproductive health and behavior. Of course, what's more about behavior than neurology? That felt like a natural place for me to focus as a clinician and especially MS, just because of the many interesting associations between reproductive experiences and MS outcomes and the many care gaps that patients face as well. Since choosing MS, I've been able to expand the scope of my research and thoughts a little bit to other aspects in this evolving socio-cultural and medical landscape, like technologies.

Cross: Great. Thanks for that. You're really an expert and you've studied and written extensively on the topic of maternal health and female hormones and such. I'm really interested to hear when you see a new or old female patient in their twenties and thirties, do you automatically discuss the potential of getting pregnant at that time, and what do you tell them?

Bove: This is an evolving landscape and we're all learning and recalibrating course along the way. But I think it's important that every time we see a person of childbearing potential, and that can be a cis woman any time from puberty to menopause and it can be any other individual of childbearing potential, these questions should be discussed. My colleagues in the field have been advancing for some time the idea of one simple question to ask at each visit. That question is: are there any plans or possibilities that you might get pregnant in the next year or a few years? This should be at the start of the MS journey, and it should be revisited at every visit along the way. And people with MS — or as we know, like anybody else, relationships can change — they can start or stop and family goals can evolve. It's really important to revisit this at each visit. I set the stage to remind patients that we will revisit it and that the goal is that there are choices to be made in terms of either supporting or preventing or delaying pregnancy, as needed, to optimize both the MS outcomes and the pregnancy outcomes.

Cross: Are women who get pregnant at increased risk if they have MS during pregnancy?

Bove: It's interesting. We don't really see that they are at increased risk of any maternal outcomes. We don't see particularly that our patients have difficulty conceiving. They may have a harder time getting pregnant perhaps because of factors like low libido or mood or fatigue. They may make specific decisions whether to get pregnant, and also the age at which patients are diagnosed may be a little later, and that may influence their childbearing goals. But we don't see that they have difficulties with any of the biological factors involved in getting pregnant. And we also don't see that they have, during pregnancy, an elevated risk of a lot of the conditions that we worry about, in terms of hypertension or diabetes or things like that. Altogether, from a biological standpoint, they don't seem to be at increased risk of difficulties during the pregnancy.

Cross: Great. That's wonderful news. So does a person, a woman planning to get pregnant, does that influence the medications for MS, the disease-modifying medications that you would consider?

Bove: It really does influence the medications that we would consider. It's important to note, again, that we're making decisions of MS therapies based on a person being able to prevent or delay pregnancy so that we can optimize the outcomes. There are specific medications that just really should not be considered in any person who might get pregnant in the coming years. The medication teriflunomide has been one that has in the past come with a big black box warning. The medications that can result in relapses, a sort of a rebound phenomenon, are also medications that we might want to avoid if they were going to be discontinued during pregnancy or before pregnancy. That would be a medication like the S1P-receptor modulators like fingolimod, or natalizumab also results in rebound relapses. But some people are making the decision to continue natalizumab at extended interval dosing throughout pregnancy. For all the other medications, it's about optimizing when to stop the medication in anticipation of the pregnancy. And if someone is on those medications with rebound potential, maybe switching them to bridge therapy to reduce the risk of that rebound potential before pregnancy. Some medications, such as the first-line self-injectable therapies like the interferons and glatiramer, they really don't seem to carry any increased risk of any adverse outcomes, even if they are continued during the pregnancy. Some clinicians and patients are thinking that that may be a good course, as well, to continue the medications right through the pregnancy.

Cross: That's great. I have found that some of my CIS (clinically isolated syndrome) patients, who have very mild disease and MRI findings and are planning to get pregnant, prefer to go on to glatiramer from the beginning just to get the childbearing years done with and then consider something a little more aggressive. Do you refer all your pregnant patients with MS to high-risk obstetricians or just some of your patients?

Bove: That's a great question. A lot of the high-risk obstetricians tell us that MS is not really a high-risk condition. The situations in which these patients might be referred is if they're older and they have co-morbidities that might otherwise influence the pregnancy or if they're on specific medications, and there's a question about continuing the medication. Then you really want joint input from the high-risk obstetricians and neurologists about the safety of different options. Or if patients have quite advanced MS and they have disabilities from their MS, that might make the pregnancy a little bit more high risk. This is, for instance, if they're not ambulatory and maybe there's a higher concern for clotting or if there's concern that labor may be a little more difficult for them. But those are the rarer exceptions. Usually, patients don't always qualify for high-risk obstetricians.

Cross: So how soon after childbirth should a woman with MS get back on her disease-modifying therapy (DMT)? And along those lines, do you recommend breastfeeding?

Bove: This question has really gotten a lot of research recently and that's exciting because while our patients with MS seem to do quite well during their pregnancy, as you know, postpartum, there is a risk of rebound disease activity. Even in patients who have clinically silent MS postpartum, there is a risk of increased new lesions and new GAD (gadolinium) lesions on MRI. There are accumulating lesions, and even if those lesions are clinically silent, eventually, of course, those lesions can contribute to neurodegeneration. Our patients who are postpartum are really in one of the highest risk categories, if you think about it, of anyone with MS in their whole MS journey. Historically, patients were advised to either start DMT right away and just don't breastfeed at all, or breastfeed and start the DMT when weaning. Breastfeeding can be an important part of a person's childbearing experience, an important part of their definition as a parent; that's not always true, and there's a lot of cultural and individual heterogeneity, but it is a goal for many of our patients. The great news is that recent studies have shown that breastfeeding exclusively in those first months postpartum is protective against inflammatory attacks. So then there is the question of, well, what to do about the DMTs? That was a question that historically we sort of steered away from and said, well, first, do no harm, so don't expose the mom and potentially the baby. But of course, that is doing harm because we're leaving our patients untreated. Recently, studies have suggested that several of these medications have minimal transfer into breast milk and minimal effects on the babies. And that includes the first-line self-injectable therapies. It also includes a lot of the monoclonal antibody therapies and there's evolving understanding of the safety of the oral therapies. In that landscape, there are medications that can be started and that are compatible with lactation. And then to your question of what to start or what to avoid, I think we're going to see that the high-efficacy medications with limited therapeutic lag — so that have rapid onset and rapid efficacy — we're going to see that those do make a difference in reducing inflammatory activity. I think I'm starting to see this in the literature, and I think we'll be able to clinch that. And if so, the advice would be breastfeed if you want, for as long as you want, and start a high-efficacy therapy early postpartum. The milk is mature by about 2 weeks postpartum, so start the high-efficacy medication. Then, there are medications that are guided by the lactation safety profile and that can include the monoclonal antibodies.

Cross: Fantastic. Do you run across postpartum depression much in women with MS and is it more common in women with MS than in the general population?

Bove: Yes, there was a nice Scandinavian study a year or two ago that did suggest that postpartum depression was more common in our patients than in the general population, and also that it's more common in specific groups. We were also able to look at this a little bit in our cohort, and some of the risk factors seem to be the same risk factors as in the general population like mood disorders prior to the pregnancy and possibly also older maternal age, first birth, and a few other factors as well. I have also run across patients who had relapse-associated depression. The postpartum relapse that they had was affective disorder relapse. But that's rare. Typically, it's just a more heightened risk of those factors like pre-pregnancy depression, and it is a concern. What's interesting anecdotally, and we're doing a prospective study on this right now, I find that the patients who don't answer the questionnaire about mood are the ones who are depressed. It's almost an indicator that we need to reach out and call them and check in on them. There is good news: the same treatments work for our patients as they do in the general population. There are several alternatives available, but it's really a question of prepping patients during pregnancy that this could be a concern; prepping their partners or other family members, that this could be a concern; and scheduling a time to check in with them postpartum to revisit that. Of course, the pediatricians and the ob/gyns are also heavily involved in screening now.

Cross: How soon do you typically see one of your patients after they've delivered?

Bove: I think it's important to see patients at least in the first 3 months. One thing that I've noticed is I can prep them as much as I can prior to the delivery but once the delivery hits, parent health is pushed aside for the benefit of the baby. And so in the United States, we know we have very short maternity leaves or parenting leaves, if any, and that's just not enough time for a person with MS to recover, do all the self-care they need to do, and really become accustomed to parenting and figure out a childcare plan for their baby. As much as possible, I try to get them to schedule that visit with me, schedule the postpartum PT (physical therapy) visit, schedule the pelvic floor PT visit during the pregnancy, make sure it's all approved by insurance so that then the hurdles to showing up are limited. Telemedicine, of course, helps us greatly in these scenarios, as we've seen over the pandemic, and I think it is important to have that check-in. Ideally, to your question, around 2 to 4 weeks postpartum, just to make sure that breastfeeding is going okay if that's part of the goal, and that the MRI and the other things are scheduled and that there hasn't been any change to our DMT resumption plan.

Cross: Telemedicine has helped these kinds of situations, especially when you have a new baby and you have to put all the paraphernalia in the car or in the Uber and have a car seat and baby's crying and has to be fed. I still remember that from having an infant … it's quite an ordeal to get them anywhere. Our guest today, Dr Bove, has done a lot of research and meta-analysis of IVF in my patients, and I'd like to ask her thoughts on that … whether it's risky or not for most patients.

Bove: So historically, it did look like there was an elevated risk of relapses in the setting of assisted reproductive technologies like IVF. Reassuringly, more recent data from several large cohorts that have been conducted in the more active MS treatment era do not reproduce this finding. Meaning, we see that patients who stay on effective therapies up until the point of their IVF seem to do really well and not relapse. I think this is important messaging for our colleagues that safe and active treatment of our patients again can support disease stability even during the high hormonal transition periods. It's also important to remind everybody that fertility treatments … there's many ways of pursuing fertility treatments other than IVF. So patients may receive embryo transfers from donor eggs or they may undergo IUI [intrauterine insemination] if they are in same-sex partnerships or have specific anatomical factors of concern. And so not all fertility treatment is the higher-risk IVF fertility treatment. And just to bear that in mind when we're advising our patients.

Cross: Do you recommend any particular types of birth control for women who may not want to get pregnant?

Bove: That's a great question. And again, it comes back to the idea that our patients have the reproductive rights to make these decisions. The LARCs, long-acting contraceptives, are really great because they reduce the behavioral aspects of birth control. They reduce all the unknowns that happen with forgetting a daily pill or using a barrier method. IUDs are particularly great for our patient population. They can stabilize some of the menstrual symptoms in terms of potentially bloating or other things that can be bothersome to our patients. And they take a lot of the guesswork out of the equation. Those are also wonderful for our younger patients who are navigating college or post-college work life and fluctuating relationships. In those settings, these LARCs can be really effective and well tolerated and a low burden for our patients.

Cross: Thank you very much for that. And I totally agree with the idea that our patients have reproductive rights that should be kept. So, is the baby of a parent with MS, especially a mother but either parent, at any increased risk and, along those lines, what would be the risk for the baby of a parent or possibly two parents with MS of getting MS themselves?

Bove: So with respect to neonatal outcomes and the immediate risks at delivery or the first years of life, some studies have suggested that the babies of a mother with MS may be perhaps a little smaller or born a little earlier, and that clinicians and/or patients may choose to use more operative-assisted modes of delivery — vacuum or caesarean, things like this — those studies really point to a very small risk. In general, the babies are born healthy and well relative to the general population. With respect to the future risks later in life of developing MS, studies have shown that having one first-degree relative increases a child's risk of developing MS to about anywhere between 1% and 5%. And with two first-degree relatives, that risk can increase to 25% or so. What I typically tell a parent, [when] the scenario is one parent with MS, there is a greater than 95% chance that the baby won't develop MS. So, what can they do about it? We know we can't change the genes, although we may be able to understand more about the epigenetic regulation. From the risk factors that have been identified in the general population in general MS epidemiology studies, it seems that maintaining a heart-healthy weight, exercising, not smoking, and ensuring that the vitamin D levels are normal or the high end of normal, those may all be protective factors. We don't know that for sure. They seem to be risk factors, we don't know whether changing them does anything, but those make sense and they're generally healthy recommendations. In the future, there may be further risk reduction once we really understand either specific nutritional components or diets or specific probiotics that may change the gut microbiome and that aspect of regulation. And then the other prevention bias, as you well know, is whether we can leverage the gains with mRNA vaccines that have been made in the COVID pandemic to demonstrate an effective vaccine against EBV, Epstein-Barr virus, the virus that causes mononucleosis. Increasingly, EBV, as you well know, appears to be necessary, even if not sufficient, to result in MS, and so the hope is that by preventing EBV infection altogether, we may be able to reduce the environment that leads to MS in the future.

Cross: Yes, that's an interesting concept. Hopefully we'll get there one day. Moving to the other end of the woman with MS life cycle — menopause. What do we tell our women going through menopause who are suffering from symptoms related to that? Do you have any encouraging thoughts on that?

Bove: That's a great question because as we know, MS begins in the "childbearing years." But if you look at the epidemiology of who is currently living with MS, about a third of all people living with MS are postmenopausal females, if not more. This is a demographic that is basically not included in the MS clinical trials. Most of the MS clinical trials have an upper age inclusion of 50 or 55 [years]. Some go beyond that, but most don't. And this is a demographic who may have different PK/PD [pharmacokinetic/pharmacodynamic] considerations or safety considerations with the MS therapies. And then of course, there's the whole interesting question of what happens to the hormones and what does that do to the MS? I think for a long time we didn't know or we didn't focus our gaze on this at all. It may have to do with the fact that by the time our female patients reached the menopausal age, they were in that progression aspect of the curve. And now that we have much more effective therapies, other questions about quality of life and perhaps more subtle questions emerge. It's a question that I get all the time, and I bet you do as well. I think there's a couple of buckets of advice or information for our patients. One is that around the age of menopause, there can be a constellation or an overlap of symptoms, of the menopausal symptoms and the MS symptoms, with respect to poor sleep or depressed mood or fatiguability, and of course bladder is a big one, and then osteoporosis. These are all things that are more common in the menopausal/postmenopausal population in general and more common in the MS population. I think the second bucket is specifically during the perimenopausal transition, or the menopausal transition, when our patients experience hot flashes, vasomotor symptoms. It's important to note that not everybody does, and even vasomotor symptoms somewhat vary according to the culture and the patient's physiology. But the hot flash symptoms, I think, do result in that Uhthoff's phenomenon, where they make other things worse. Of course, if they're happening at night, they can interrupt sleep and just make everything about MS, and living in general, worse. So the hot flashes are a specific symptom that there are many treatments for in general, both hormonal treatments and nonhormonal treatments, and it's important to tackle those because of their domino effects on a patient's well-being. The next bucket is whether, postmenopausally, anything about the changing hormonal dynamic affects potential for myelin repair or potential for neurodegeneration and what to do about that. I think that's an area where we have a few studies and kind of evolving guidance. It's still unclear. Perhaps at worst, patients have a little bit of worsening postmenopausally relative to the expected slope premenopausally. And then finally, the fourth bucket … the need to do more research here. It's a big chunk of our patient population and we owe it to our patients to know a lot more.

Cross: Great. Do you have any specific nonhormonal, like homeopathic, remedies that you recommend to women going through menopause?

Bove: I talk about the lifestyle factors. In general, wear layers, being in a heart-healthy way premenopausally, and not smoking … all those behavioral factors. In terms of the nonhormonal medications, the ones that have been shown to be helpful, are some of the antidepressants, venlafaxine to name one. But there are others that have shown to be effective as well. Sometimes people have benefits from medications like gabapentin. I recommend that that be a conversation between the patient and either their primary care physician or their gynecologist. With respect to homeopathic or natural, in general, I think that the science is always a little bit less well done in those situations, unfortunately. Because of that, I don't really have enough knowledge or certainty to make any specific recommendations.

Cross: Thank you very much for that. And I have to say, I've learned a huge amount today from Dr Bove. This has been a wonderful session. I would say that the key takeaways I got were that, number one, it's safe for women with MS to get pregnant and have children and the children are typically normal. We just have to plan in advance. She mentioned the one simple question that she tends to ask women of childbearing age when they come in about plans for pregnancy. She also mentioned that long-acting contraceptives are particularly good, such as IUDs. And along those lines, I think she and I both support the idea of reproductive rights for our patients with MS. And finally, we wrapped up with the situation of menopause and the symptoms that women with MS and other women will have, and some concrete ideas on how to handle those for our patients. I really, really appreciate Dr Riley Bove for joining us today on this podcast, and I hope our audience has gotten as much out of it as I have. This is Dr Anne Cross for InDiscussion.


Multiple Sclerosis

Teriflunomide (Rx)

Sphingosine 1-Phosphate Receptor Modulators

Natalizumab Prescribing Information

Association Between Breastfeeding and Postpartum Multiple Sclerosis Relapses

Perinatal Depression and Anxiety in Women With Multiple Sclerosis

Risk Factors for Peripartum Depression in Women With Multiple Sclerosis

Long-Acting Reversible Contraception: Comparing Methods

Neonatal and Delivery Outcomes in Women With Multiple Sclerosis

A Genetic Basis for Familial Aggregation in Multiple Sclerosis

Familial Risk of Early- and Late-Onset Multiple Sclerosis: A Swedish Nationwide Study

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